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Alzheimer's & Dementia : the Journal of... Jun 2024We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities.
Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities in a community-dwelling cohort.
INTRODUCTION
We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities.
METHODS
We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aβ] 42/40, phosphorylated tau 181) and neuroimaging measures of amyloid deposition (Aβ-positron emission tomography [PET]), total brain volume, white matter hyperintensity volume, diffusion-weighted fractional anisotropy, and neurite orientation dispersion and density imaging free water. Participants were adjudicated as cognitively unimpaired (CU; N = 299), mild cognitive impairment (MCI; N = 192), or dementia (DEM; N = 65). Biomarkers were compared across groups stratified by diagnosis, sex, race, and APOE ε4 carrier status. General linear models examined plasma-imaging associations before and after adjusting for demographics (age, sex, race, education), APOE ε4 status, medications, diagnosis, and other factors (estimated glomerular filtration rate [eGFR], body mass index [BMI]).
RESULTS
Plasma biomarkers differed across diagnostic groups (DEM > MCI > CU), were altered in Aβ-PET-positive individuals, and were associated with poorer brain health and kidney function.
DISCUSSION
eGFR and BMI did not substantially impact associations between plasma and neuroimaging biomarkers.
HIGHLIGHTS
Plasma biomarkers differ across diagnostic groups (DEM > MCI > CU) and are altered in Aβ-PET-positive individuals. Altered plasma biomarker levels are associated with poorer brain health and kidney function. Plasma and neuroimaging biomarker associations are largely independent of comorbidities.
Topics: Humans; Male; Female; Positron-Emission Tomography; Biomarkers; Aged; Alzheimer Disease; Magnetic Resonance Imaging; Amyloid beta-Peptides; Comorbidity; Brain; Dementia; tau Proteins; Cohort Studies; Independent Living; Cognitive Dysfunction; Middle Aged; Neuroimaging
PubMed: 38747525
DOI: 10.1002/alz.13835 -
BioRxiv : the Preprint Server For... May 2024Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological...
Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1±6.6 years old, 125 females). We show that body height correlated strongly or moderately with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44≤r≤0.62). In comparison, age correlated weakly with cortical GM volume, precentral GM volume, and cortical thickness (-0.21≥r≥-0.27). Body weight correlated weakly with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20≥r≥-0.23). Body weight further correlated weakly with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r=-0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlated strongly or moderately with brain volumes (0.39≤r≤0.64), and weakly with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22≥r≥-0.25). Linear mixture of sex and age explained 26±10% of data variance in brain volumetry and SC CSA. The amount of explained variance increased at 33±11% when body height was added into the mixture model. Age itself explained only 2±2% of such variance. In conclusion, body size is a significant biological variable. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure.
PubMed: 38746371
DOI: 10.1101/2024.04.29.591421 -
Scientific Reports May 2024Biological sex is a crucial variable in neuroscience studies where sex differences have been documented across cognitive functions and neuropsychiatric disorders. While...
Biological sex is a crucial variable in neuroscience studies where sex differences have been documented across cognitive functions and neuropsychiatric disorders. While gross statistical differences have been previously documented in macroscopic brain structure such as cortical thickness or region size, less is understood about sex-related cellular-level microstructural differences which could provide insight into brain health and disease. Studying these microstructural differences between men and women paves the way for understanding brain disorders and diseases that manifest differently in different sexes. Diffusion MRI is an important in vivo, non-invasive methodology that provides a window into brain tissue microstructure. Our study develops multiple end-to-end classification models that accurately estimates the sex of a subject using volumetric diffusion MRI data and uses these models to identify white matter regions that differ the most between men and women. 471 male and 560 female healthy subjects (age range, 22-37 years) from the Human Connectome Project are included. Fractional anisotropy, mean diffusivity and mean kurtosis are used to capture brain tissue microstructure characteristics. Diffusion parametric maps are registered to a standard template to reduce bias that can arise from macroscopic anatomical differences like brain size and contour. This study employ three major model architectures: 2D convolutional neural networks, 3D convolutional neural networks and Vision Transformer (with self-supervised pretraining). Our results show that all 3 models achieve high sex classification performance (test AUC 0.92-0.98) across all diffusion metrics indicating definitive differences in white matter tissue microstructure between males and females. We further use complementary model architectures to inform about the pattern of detected microstructural differences and the influence of short-range versus long-range interactions. Occlusion analysis together with Wilcoxon signed-rank test is used to determine which white matter regions contribute most to sex classification. The results indicate that sex-related differences manifest in both local features as well as global features / longer-distance interactions of tissue microstructure. Our highly consistent findings across models provides new insight supporting differences between male and female brain cellular-level tissue organization particularly in the central white matter.
Topics: Humans; Deep Learning; White Matter; Male; Female; Adult; Diffusion Magnetic Resonance Imaging; Young Adult; Sex Characteristics; Brain; Connectome; Image Processing, Computer-Assisted
PubMed: 38744901
DOI: 10.1038/s41598-024-60340-y -
Medical Science Monitor : International... May 2024BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network... (Comparative Study)
Comparative Study
Correlation between Thalamocortical Tract and Default Mode Network with Consciousness Levels in Hypoxic-Ischemic Brain Injury Patients: A Comparative Study Using the Coma Recovery Scale-Revised.
BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network (DMN) comprises bilateral, symmetrical, isolated cortical regions of the lateral and medial parietal and temporal brain cortex. The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment of disorders of consciousness (DOC). In the present study, 31 patients with hypoxic-ischemic brain injury (HI-BI) were compared for changes in the TCT and DMN with consciousness levels assessed using the CRS-R. MATERIAL AND METHODS In this retrospective study, 31 consecutive patients with HI-BI (17 DOC,14 non-DOC) and 17 age- and sex-matched normal control subjects were recruited. Magnetic resonance imaging was used to diagnose HI-BI, and the CRS-R was used to evaluate consciousness levels at the time of diffusion tensor imaging (DTI). The fractional anisotropy (FA) values and tract volumes (TV) of the TCT and DMN were compared. RESULTS In patients with DOC, the FA values and TV of both the TCT and DMN were significantly lower compared to those of patients without DOC and the control subjects (p<0.05). When comparing the non-DOC and control groups, the TV of the TCT and DMN were significantly lower in the non-DOC group (p<0.05). Moreover, the CRS-R score had strong positive correlations with the TV of the TCT (r=0.501, p<0.05), FA of the DMN (r=0.532, p<0.05), and TV of the DMN (r=0.501, p<0.05) in the DOC group. CONCLUSIONS This study suggests that both the TCT and DMN exhibit strong correlations with consciousness levels in DOC patients with HI-BI.
Topics: Humans; Female; Male; Middle Aged; Thalamus; Hypoxia-Ischemia, Brain; Adult; Consciousness; Diffusion Tensor Imaging; Cerebral Cortex; Retrospective Studies; Coma; Magnetic Resonance Imaging; Default Mode Network; Consciousness Disorders; Aged
PubMed: 38741355
DOI: 10.12659/MSM.943802 -
Neuro-oncology Practice Jun 2024The microstructural damage underlying compromise of white matter following treatment for pediatric brain tumors is unclear. We use multimodal imaging employing advanced...
BACKGROUND
The microstructural damage underlying compromise of white matter following treatment for pediatric brain tumors is unclear. We use multimodal imaging employing advanced diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) MRI methods to examine chronic microstructural damage to white matter in children and adolescents treated for pediatric brain tumor. Notably, MTI may be more sensitive to macromolecular content, including myelin, than DTI.
METHODS
Fifty patients treated for brain tumors (18 treated with surgery ± chemotherapy and 32 treated with surgery followed by cranial-spinal radiation; time from diagnosis to scan ~6 years) and 45 matched healthy children completed both MTI and DTI scans. Voxelwise and region-of-interest approaches were employed to compare white matter microstructure metrics (magnetization transfer ratio (MTR); DTI- fractional anisotropy [FA], radial diffusivity [RD], axial diffusivity [AD], mean diffusivity [MD]) between patients and healthy controls.
RESULTS
MTR was decreased across multiple white matter tracts in patients when compared to healthy children, < .001. These differences were observed for both patients treated with radiation and those treated with only surgery, < .001. We also found that children and adolescents treated for brain tumors exhibit decreased FA and increased RD/AD/MD compared to their healthy counterparts in several white matter regions, s < .02. Finally, we observed that MTR and DTI metrics were related to multiple white matter tracts in patients, s < .01, but not healthy control children.
CONCLUSIONS
Our findings provide evidence that the white matter damage observed in patients years after treatment of pediatric posterior fossa tumors, likely reflects myelin disruption.
PubMed: 38737604
DOI: 10.1093/nop/npae003 -
Frontiers in Neuroscience 2024In recent years, there has been a growing interest in studying the Superficial White Matter (SWM). The SWM consists of short association fibers connecting near giry of...
In recent years, there has been a growing interest in studying the Superficial White Matter (SWM). The SWM consists of short association fibers connecting near giry of the cortex, with a complex organization due to their close relationship with the cortical folding patterns. Therefore, their segmentation from dMRI tractography datasets requires dedicated methodologies to identify the main fiber bundle shape and deal with spurious fibers. This paper presents an enhanced short fiber bundle segmentation based on a SWM bundle atlas and the filtering of noisy fibers. The method was tuned and evaluated over HCP test-retest probabilistic tractography datasets (44 subjects). We propose four fiber bundle filters to remove spurious fibers. Furthermore, we include the identification of the main fiber fascicle to obtain well-defined fiber bundles. First, we identified four main bundle shapes in the SWM atlas, and performed a filter tuning in a subset of 28 subjects. The filter based on the Convex Hull provided the highest similarity between corresponding test-retest fiber bundles. Subsequently, we applied the best filter in the 16 remaining subjects for all atlas bundles, showing that filtered fiber bundles significantly improve test-retest reproducibility indices when removing between ten and twenty percent of the fibers. Additionally, we applied the bundle segmentation with and without filtering to the ABIDE-II database. The fiber bundle filtering allowed us to obtain a higher number of bundles with significant differences in fractional anisotropy, mean diffusivity, and radial diffusivity of Autism Spectrum Disorder patients relative to controls.
PubMed: 38737100
DOI: 10.3389/fnins.2024.1394681 -
Frontiers in Neuroscience 2024Effects of dioxin exposure on gray matter volume have been reported in previous studies, but a few studies reported effects of dioxin exposure on white matter structure....
INTRODUCTION
Effects of dioxin exposure on gray matter volume have been reported in previous studies, but a few studies reported effects of dioxin exposure on white matter structure. Therefore, this study was undertaken to investigate the impact of dioxin exposure on white matter microstructure in men living in the most severely dioxin-contaminated areas in Vietnam.
METHODS
In 2019 brain MRI scans from 28 men living near Bien Hoa airbase were obtained at Dong Nai General Hospital, Vietnam, on a 3 T scanner using a conventional diffusion tensor imaging sequence. Two exposure markers were indicated by perinatal exposure estimated by assessment of maternal residency in a dioxin-contaminated area during pregnancy and by measurement of blood dioxin levels. A general linear model was used to compare fractional anisotropy (FA) values in 11 white matter tracts in both hemispheres between groups with and without perinatal dioxin exposure and groups with high and low blood dioxin levels after adjusting for covariates.
RESULTS
The adjusted mean FA value in the left cingulum hippocampal part (CGH) was significantly lower in the perinatal dioxin exposure group compared with the group without perinatal dioxin exposure. The high blood TCDD group showed significantly reduced FA values in the left and right CGH and right uncinate fasciculus (UNC). Moreover, the high blood TEQ-PCDDs group showed significantly lower FA values in the left and right CGH and the left UNC. There were no significant differences in FA values between the groups with high and low TEQ-PCDFs levels or between the groups with high and low TEQ-PCDD/Fs levels.
DISCUSSION
It was concluded that dioxin exposure during the perinatal period and adulthood may alter the microstructure of white matter tracts in individuals with neurodevelopmental disorders.
PubMed: 38726030
DOI: 10.3389/fnins.2024.1344653 -
ENeuro May 2024The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions...
The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by cardiovascular risk factors, which negatively influence white matter health. Here, we test for heterochronicity of aging, hypothesizing an anteroposterior gradient of vulnerability to aging that may be altered by the effects of cardiovascular health. In 174 healthy adults across the adult lifespan (mean age = 53.56 ± 18.90; range, 20-94 years old, 58.62% women), pulse pressure (calculated as participant's systolic minus diastolic blood pressure) was assessed to determine cardiovascular risk. A deterministic tractography approach via diffusion-weighted imaging was utilized to extract fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) from each of five callosal subregions, serving as estimates of microstructural health. General linear models tested the effects of age, hypertension, and pulse pressure on these cross-sectional metrics. We observed no significant effect of hypertensive diagnosis on callosal microstructure. We found a significant main effect of age and an age-pulse pressure interaction whereby older age and elevated pulse pressure were associated with poorer FA, AD, and RD. Age effects revealed nonlinear components and occurred along an anteroposterior gradient of severity in the callosum. This gradient disappeared when pulse pressure was considered. These results indicate that age-related deterioration across the callosum is regionally variable and that pulse pressure, a proxy of arterial stiffness, exacerbates this aging pattern in a large lifespan cohort.
Topics: Humans; Corpus Callosum; Female; Middle Aged; Aged; Adult; Male; Aging; Aged, 80 and over; Young Adult; Blood Pressure; Diffusion Tensor Imaging; Hypertension; Cross-Sectional Studies; Diffusion Magnetic Resonance Imaging
PubMed: 38719452
DOI: 10.1523/ENEURO.0449-23.2024 -
Human Brain Mapping May 2024The global ageing of populations calls for effective, ecologically valid methods to support brain health across adult life. Previous evidence suggests that music can...
The global ageing of populations calls for effective, ecologically valid methods to support brain health across adult life. Previous evidence suggests that music can promote white matter (WM) microstructure and grey matter (GM) volume while supporting auditory and cognitive functioning and emotional well-being as well as counteracting age-related cognitive decline. Adding a social component to music training, choir singing is a popular leisure activity among older adults, but a systematic account of its potential to support healthy brain structure, especially with regard to ageing, is currently missing. The present study used quantitative anisotropy (QA)-based diffusion MRI connectometry and voxel-based morphometry to explore the relationship of lifetime choir singing experience and brain structure at the whole-brain level. Cross-sectional multiple regression analyses were carried out in a large, balanced sample (N = 95; age range 21-88) of healthy adults with varying levels of choir singing experience across the whole age range and within subgroups defined by age (young, middle-aged, and older adults). Independent of age, choir singing experience was associated with extensive increases in WM QA in commissural, association, and projection tracts across the brain. Corroborating previous work, these overlapped with language and limbic networks. Enhanced corpus callosum microstructure was associated with choir singing experience across all subgroups. In addition, choir singing experience was selectively associated with enhanced QA in the fornix in older participants. No associations between GM volume and choir singing were found. The present study offers the first systematic account of amateur-level choir singing on brain structure. While no evidence for counteracting GM atrophy was found, the present evidence of enhanced structural connectivity coheres well with age-typical structural changes. Corroborating previous behavioural studies, the present results suggest that regular choir singing holds great promise for supporting brain health across the adult life span.
Topics: Humans; Adult; Male; Middle Aged; Aged; Female; Young Adult; Singing; Aged, 80 and over; White Matter; Aging; Cross-Sectional Studies; Brain; Gray Matter; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging
PubMed: 38716698
DOI: 10.1002/hbm.26705 -
Brain Communications 2024Delirium, memory loss, attention deficit and fatigue are frequently reported by COVID survivors, yet the neurological pathways underlying these symptoms are not well...
Delirium, memory loss, attention deficit and fatigue are frequently reported by COVID survivors, yet the neurological pathways underlying these symptoms are not well understood. To study the possible mechanisms for these long-term sequelae after COVID-19 recovery, we investigated the microstructural properties of white matter in Indian cohorts of COVID-recovered patients and healthy controls. For the cross-sectional study presented here, we recruited 44 COVID-recovered patients and 29 healthy controls in New Delhi, India. Using deterministic whole-brain tractography on the acquired diffusion MRI scans, we traced 20 white matter tracts and compared fractional anisotropy, axial, mean and radial diffusivity between the cohorts. Our results revealed statistically significant differences ( < 0.01) in the uncinate fasciculus, cingulum cingulate, cingulum hippocampus and arcuate fasciculus in COVID survivors, suggesting the presence of microstructural abnormalities. Additionally, in a subsequent subgroup analysis based on infection severity (healthy control, non-hospitalized patients and hospitalized patients), we observed a correlation between tract diffusion measures and COVID-19 infection severity. Although there were significant differences between healthy controls and infected groups, we found no significant differences between hospitalized and non-hospitalized COVID patients. Notably, the identified tracts are part of the limbic system and orbitofrontal cortex, indicating microstructural differences in neural circuits associated with memory and emotion. The observed white matter alterations in the limbic system resonate strongly with the functional deficits reported in Long COVID. Overall, our study provides additional evidence that damage to the limbic system could be a neuroimaging signature of Long COVID. The findings identify targets for follow-up studies investigating the long-term physiological and psychological impact of COVID-19.
PubMed: 38715715
DOI: 10.1093/braincomms/fcae139